IGF-I receptors regulate the growth-promoting and differentiative effects of IGF-I and IGF-II. The IGF-I recpetor, though encoded by a separate gene, is structurally and functionally related to the insulin receptor, both being transmembrane tyrosine kinases. To investigate structure/function relationships in the IGF-I receptor, we have used a number of different techniques, inclduding (A) isolation and characterization of the proximal promoter for the human and rat IGF-I receptor genes, (B) mutagenesis of the tyrosine kinase domain of the human IGF-I receptor and (C) analysis of post-receptors events. These studies should contribute to our understanding of the role of IGFs and the IGF receptor in health and disease.